EP2762854A2 - Mikrogeformte Zytometerkartusche mit integrierter Optik - Google Patents

Mikrogeformte Zytometerkartusche mit integrierter Optik Download PDF

Info

Publication number
EP2762854A2
EP2762854A2 EP14151333.3A EP14151333A EP2762854A2 EP 2762854 A2 EP2762854 A2 EP 2762854A2 EP 14151333 A EP14151333 A EP 14151333A EP 2762854 A2 EP2762854 A2 EP 2762854A2
Authority
EP
European Patent Office
Prior art keywords
micro
approximately
channel
measurement channel
microns
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP14151333.3A
Other languages
English (en)
French (fr)
Other versions
EP2762854B1 (de
EP2762854A3 (de
Inventor
Ronald Bardell
Jeffrey Shonkwiler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Honeywell International Inc
Original Assignee
Honeywell International Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Honeywell International Inc filed Critical Honeywell International Inc
Publication of EP2762854A2 publication Critical patent/EP2762854A2/de
Publication of EP2762854A3 publication Critical patent/EP2762854A3/de
Application granted granted Critical
Publication of EP2762854B1 publication Critical patent/EP2762854B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1484—Optical investigation techniques, e.g. flow cytometry microstructural devices

Definitions

  • the present disclosure relates to cytometers, and in an embodiment, but not by way of limitation, a micro-molded cytometer cartridge with integrated optics.
  • Current cytometer cartridges have several limitations. Current cytometer cartridges require two orders of magnitude more sheath fluid than sample fluid. This volume of sheath fluid makes up most of the waste fluid and requires a relatively large cartridge size. Current cytometer cartridges require an optical system that resides on the cytometer instrument and that precisely aligns with the cytometer instrument and the illumination source and detectors of the instrument. Current cartridges further need to be able to search for, and lock onto, the stream of cells within the measurement channel. Current cartridges limit the range of scatter angles that can be detected to those angles that are much smaller than 30 degrees. Current cartridges require a precise sample via to inject sample into the reagent channel. Additionally, the dimensional tolerance of the sample via is one of the smallest on the cytometer cartridge card.
  • a micro-molded component in a cytometer cartridge insert, includes a measurement channel and one or more integrated optical lenses with alignment features.
  • the micro-molded component is embedded in a cytometer cartridge that is a plastic laminate cartridge.
  • the alignment features ensure alignment between the integrated optical system on the cartridge and the light source and detectors on the instrument (i.e., via the manifold of the cytometer instrument).
  • the micro-molding process ensures that the measurement channel walls of the integrated optical system have a low RMS planarity level and good optical finish characteristics.
  • the light scatter from the illumination beam on the walls has the same group of angles as the beam and thus occupies only a small solid angle of the total budget of angles and will not produce random scatter noise.
  • the integrated optical lenses also allow detection of scatter angles as large as 90 degrees. As is known in the art, a larger scatter angle provides more information about the cells and easier differentiation among cell types.
  • the micro-molded component also includes other small tolerance features of the cartridge insert, such as a hemoglobin measuring cuvette and a sample via.
  • the micro-molded component can be produced with a lower manufacturing cost of the plastic laminate cartridge.
  • the relatively small footprint of the micro-molded component in relation to its thickness allows manufacture of the component using injection molding. In contrast, the use of injection molding for a full card layer would result in a relatively inefficient fabrication process.
  • a micro-molded insert for the proposed cytometer cartridge includes a measurement channel (e.g ., having a diameter ranging from 20 microns to 200 microns) with integrated optical lenses, a sample via, and a hemoglobin measuring cuvette.
  • the molded component is integrated into a plastic laminate cartridge containing a sample tank, a lysing/sphering channel, a hemoglobin reagent channel, and waste chamber.
  • Fixed laser and optical detectors are mounted in a rigid manifold in the cytometer instrument. When the cartridge is loaded into the instrument, registration surfaces on the micro-molded insert contact similar registration surfaces on the laser and detector assembly of the cytometer instrument for precise positioning.
  • sheathing fluid need not be used in connection with the cytometer cartridge insert.
  • the sample via causes the lysing and sphering solutions to sheath the sample fluid sufficiently so that the blood cells are focused to flow near the center of the channel.
  • the integrated optical system and the small diameter of the measurement channel ensure that all cells are interrogated by the laser. Consequently, a typical cytometer protocol applies, except that there is no sheathing fluid to start up prior to counting cells, so there are no sheath fluid bubbles to clear, and since the laser and detectors are registered to the micro-molded insert in the cartridge, there is no laser alignment step.
  • optical lenses are implemented as part of the measurement channel, they can be precisely oriented for scatter detection at optimal angles, for example, within 2-9 degrees, within 9-20 degrees, and at 90 degrees.
  • the hemoglobin measuring cuvette, which has a tight tolerance on its optical path length dimension, and the sample via, which has a tight tolerance on its diameter and position, are both implemented in the micro-molded insert.
  • FIG. 1 illustrates an example embodiment of a micro-molded cytometer cartridge with integrated optics.
  • the cartridge includes a micro-molded component 100 and a plastic laminate component 103.
  • the micro-molded component 100 is embedded in the plastic laminate component 103.
  • the micro-molded component 100 includes several features.
  • the sample via 110 transmits blood sample from channel 125 to channel 115.
  • the sample via 110 has a diameter ranging from approximately 30 microns to approximately 100 microns. The ability to manufacture a sample via of this size is possible by using micro-molding techniques.
  • the micro-molded component 100 further includes a measurement channel 130 with integrated optical lenses 135.
  • the measurement channel 130 is coupled to the sample via 110 by way of a lysing and sphering channel 115.
  • the measurement channel 130 has a diameter ranging from approximately 20 microns to approximately 200 microns.
  • the length of the measurement channel 130 can range from about 100 microns to 2500 microns.
  • the diameter of the sample via 110 and the measurement channel 130 permits the use of no sheathing fluid, and the diameter further results in a single stream of cells.
  • the micro-molded component 100 also includes a cuvette 120.
  • the cuvette is a hemoglobin measuring cuvette. Blood or other sample is supplied to the cuvette 120 by way of a channel 123.
  • the channel 123 is also coupled to the same source of sample as channel 125.
  • Both the sample via 110 and the cuvette 120 contain the same sample.
  • the cuvette 120 can range in diameter from about 250 microns to about 3500 microns.
  • the cuvette 120 has an optical mask around it on the light detector side so as to block any light scatter.
  • the cytometer cartridge includes an alignment device 140 for aligning the integrated optical lens with a light source and a light detector.
  • the light source and the light detector are normally located on the cytometer instrument.
  • the alignment device is a three-point registration surface, which is configured or manufactured to couple with a mating registration surface of a manifold of the cytometer instrument.
  • the integrated optical lens 135 is aligned with the measurement channel such that the light scatter from the illumination beam on the optically-smooth measurement channel walls occupies only a small solid angle of the total budget of angles and will not produce random scatter noise.
  • the plastic laminate component 103 includes a waste chamber 150.
  • the waste chamber 150 is coupled to the cuvette 120 and the measurement channel 130, such that it serves as a receptacle for the sample after it has been analyzed in the cuvette or measurement channel.
  • the micro-molding manufacture of the cartridge 100 permits a very small scale manufacture of the sample via 110, measurement channel 130, cuvette 120, and other related components.
  • the waste chamber has a volume of approximately 3 milliliters.
  • the plastic laminate component 103 further includes a lysing and sphering channel, a reagent channel, and a sample tank.
  • FIG. 2 is a flowchart of an example embodiment of a process 200 to manufacture a cytometer cartridge with integrated optics.
  • FIG. 2 includes a number of process and feature blocks 205 - 260. Though arranged substantially serially in the example of FIG. 2 , other examples may reorder the blocks, omit one or more blocks, and/or execute two or more blocks in parallel using multiple processors or a single processor organized as two or more virtual machines or sub-processors. Moreover, still other examples can implement the blocks as one or more specific interconnected hardware or integrated circuit modules with related control and data signals communicated between and through the modules. Thus, any process flow is applicable to software, firmware, hardware, and hybrid implementations.
  • a cytometer cartridge insert is manufactured by forming a plastic laminate component, and at 220, embedding a micro-molded component in the plastic laminate component.
  • a sample via is formed in the micro-molded component such that the diameter of the sample via ranges from approximately 20 microns to approximately 100 microns.
  • a measurement channel is formed in the micro-molded component such that a diameter of the measurement channel ranges from approximately 20 microns to approximately 200 microns.
  • an integrated optical lens is formed in the measurement channel.
  • a cuvette is formed in the micro-molded component. As noted above, the cuvette is coupled to a sample channel that is also coupled to the sample via. As noted in block 235, the cuvette can be for measuring hemoglobin.
  • a lysing and sphering channel is formed in the plastic laminate component. The lysing and sphering channel couple the measurement channel to the sample via.
  • an alignment device is formed in the micro-molded component.
  • the alignment device is manufactured or configured to align the integrated optical lens with a light source and a light detector.
  • a registration surface is formed on the alignment device.
  • the registration surface is manufactured or configured for coupling with a registration surface of a manifold of a cytometer instrument.
  • the integrated optical lens is aligned with the measurement channel such that the measurement channel walls do not produce random scatter noise. As noted above, this alignment of the optical lens and measurement channel insures that light scatter from the illumination beam on the optically-smooth measurement channel walls occupies only a small solid angle of the total budget of angles and will not produce random scatter noise.
  • a waste chamber is formed on the plastic laminate component such that the waste chamber is coupled to the cuvette and the measurement channel.
  • the waste chamber has a volume of approximately 3 milliliters. This small volume is made possible by the reduced size of the micro-molded components compared to prior art cytometers.
  • a_lysing and sphering channel, a reagent channel, and a sample tank are formed in the plastic laminate component.
  • the micro-molded component is formed by injection molding, soft-embossing, or hot-embossing.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Dispersion Chemistry (AREA)
  • Optical Measuring Cells (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Laminated Bodies (AREA)
EP14151333.3A 2013-01-31 2014-01-15 Mikrogeformte zytometerkartusche mit integrierter optik Active EP2762854B1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US13/755,536 US9207166B2 (en) 2013-01-31 2013-01-31 Micro-molded cytometer cartridge with integrated optics

Publications (3)

Publication Number Publication Date
EP2762854A2 true EP2762854A2 (de) 2014-08-06
EP2762854A3 EP2762854A3 (de) 2017-12-27
EP2762854B1 EP2762854B1 (de) 2021-03-31

Family

ID=49999737

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14151333.3A Active EP2762854B1 (de) 2013-01-31 2014-01-15 Mikrogeformte zytometerkartusche mit integrierter optik

Country Status (3)

Country Link
US (1) US9207166B2 (de)
EP (1) EP2762854B1 (de)
CN (1) CN103969170B (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10634602B2 (en) 2015-06-12 2020-04-28 Cytochip Inc. Fluidic cartridge for cytometry and additional analysis
CN108025904B (zh) * 2015-06-12 2021-10-15 芯易诊有限公司 用于多分析物分析的流体单元和流体卡式盒
US10641698B2 (en) 2015-06-12 2020-05-05 Cytochip Inc. Methods for complete blood count measurement
EP3535056B1 (de) * 2016-11-07 2024-12-11 Cytochip Inc. Fluidkartusche für zytometrie und zusätzliche analyse
WO2018098142A1 (en) * 2016-11-22 2018-05-31 Cytochip Inc. Methods for complete blood count measurement
CN110199186B (zh) * 2016-11-22 2023-01-10 芯易诊有限公司 全血细胞计数测量方法
WO2019083844A1 (en) 2017-10-23 2019-05-02 Cytochip Inc. DEVICES AND METHOD FOR MEASURING TARGET ANALYTES AND PARTICLES
CN214895849U (zh) 2021-01-28 2021-11-26 贝克曼库尔特生物科技（苏州）有限公司 气泡检测装置和样本处理仪
US12564837B2 (en) 2021-02-05 2026-03-03 Cytek Biosciences, Inc. Integrated compact cell sorter
CN113552030B (zh) * 2021-07-19 2023-01-31 国家海洋技术中心 一种投弃式海洋微塑料浓度现场测量装置及方法

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2320296A1 (en) 1998-05-18 1999-11-25 University Of Washington Liquid analysis cartridge
US20050077175A1 (en) * 1999-06-16 2005-04-14 Friedhelm Eisenbeiss Miniaturized analytical system
US6687395B1 (en) 1999-07-21 2004-02-03 Surromed, Inc. System for microvolume laser scanning cytometry
US7242474B2 (en) * 2004-07-27 2007-07-10 Cox James A Cytometer having fluid core stream position control
US6597438B1 (en) 2000-08-02 2003-07-22 Honeywell International Inc. Portable flow cytometry
US7420659B1 (en) * 2000-06-02 2008-09-02 Honeywell Interantional Inc. Flow control system of a cartridge
US7978329B2 (en) 2000-08-02 2011-07-12 Honeywell International Inc. Portable scattering and fluorescence cytometer
US7630063B2 (en) 2000-08-02 2009-12-08 Honeywell International Inc. Miniaturized cytometer for detecting multiple species in a sample
US7000330B2 (en) * 2002-08-21 2006-02-21 Honeywell International Inc. Method and apparatus for receiving a removable media member
US6382228B1 (en) 2000-08-02 2002-05-07 Honeywell International Inc. Fluid driving system for flow cytometry
WO2002081934A2 (en) * 2001-04-03 2002-10-17 Micronics, Inc. Pneumatic valve interface for use in microfluidic structures
US6880414B2 (en) 2002-08-08 2005-04-19 Becton Dickinson And Company Sort block and liquid collection device for sorting flow cytometer
BRPI0408857B1 (pt) * 2003-03-28 2018-09-11 Inguran Llc aparelho, métodos e processos para separar partículas e para prover esperma de animal separado por sexo
US7767435B2 (en) * 2003-08-25 2010-08-03 University Of Washington Method and device for biochemical detection and analysis of subcellular compartments from a single cell
US8189899B2 (en) 2004-07-30 2012-05-29 Veridex, Llc Methods and algorithms for cell enumeration in a low-cost cytometer
JP2007003414A (ja) * 2005-06-24 2007-01-11 Arkray Inc 分析装置用カートリッジ
JP4995197B2 (ja) 2005-07-01 2012-08-08 ハネウェル・インターナショナル・インコーポレーテッド ３ｄ流体力学的集束を有する成形カートリッジ
JP5431732B2 (ja) * 2005-12-29 2014-03-05 ハネウェル・インターナショナル・インコーポレーテッド マイクロ流体フォーマットにおけるアッセイ実装
US9810707B2 (en) 2006-05-17 2017-11-07 Luminex Corporation Chip-based flow cytometer type systems for analyzing fluorescently tagged particles
US20120225475A1 (en) 2010-11-16 2012-09-06 1087 Systems, Inc. Cytometry system with quantum cascade laser source, acoustic detector, and micro-fluidic cell handling system configured for inspection of individual cells
US20120258488A1 (en) 2011-04-11 2012-10-11 The Regents Of The University Of California Systems and Methods for Electrophysiological Activated Cell Sorting and Cytometry

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None

Also Published As

Publication number Publication date
US9207166B2 (en) 2015-12-08
CN103969170B (zh) 2018-02-13
EP2762854B1 (de) 2021-03-31
CN103969170A (zh) 2014-08-06
US20140211205A1 (en) 2014-07-31
EP2762854A3 (de) 2017-12-27

Similar Documents

Publication Publication Date Title
US9207166B2 (en) Micro-molded cytometer cartridge with integrated optics
JP7588029B2 (ja) サンプル検査のための装置、システムおよび方法
US10301676B2 (en) Nucleic acid sequencing system
AU2003232169B2 (en) A disposable cartridge for characterizing particles suspended in a liquid
CN102393705B (zh) 样本有形成分分析仪自动检测控制装置及其控制方法
WO2012051206A1 (en) System and method for cell analysis
WO2013099078A1 (en) Microchip and microchip-type fine-particle measuring device
EP2536818A1 (de) Immunmultiplex-assay mit immobilisierten perlen
KR20190029584A (ko) 샘플의 이미지 기반 분석
Shanmugam et al. Lensless fluorescence imaging with height calculation
JP2022141675A (ja) 光散乱検出器及び光散乱検出器のための方法
US12540894B2 (en) Position adjusting method, microparticle analysis device, and program
US9970875B2 (en) Sensor chip for SPFS measurement, SPFS measurement method using sensor chip for SPFS measurement, and SPFS measurement device equipped with sensor chip for SPFS measurement
CN101581660A (zh) 通道基板
Su et al. Smart palm-size optofluidic hematology analyzer for automated imaging-based leukocyte concentration detection
CN113008786A (zh) 血液细胞分析仪
US20180067288A1 (en) Device for measuring solution concentration
KR20190023438A (ko) 광섬유를 이용한 유세포 분석 시스템
US20250258088A1 (en) Concentration measurement device
CN107356770A (zh) 一种全自动表面等离子体共振检测仪
CN116171379A (zh) 用于分析组分的h-型过滤器装置
CN217359605U (zh) 一种血液分析仪的光学系统及血液分析仪
CN219475615U (zh) 样本分析仪
CN219475616U (zh) 样本分析仪
Elizalde et al. Multi-parametric point of care device for allergen-specific IgE detection in veterinary applications

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20140115

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: HONEYWELL INTERNATIONAL INC.

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 15/14 20060101AFI20171123BHEP

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20180202

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20201125

RIN1 Information on inventor provided before grant (corrected)

Inventor name: SHONKWILER, JEFFREY

Inventor name: BARDELL, RONALD

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1377490

Country of ref document: AT

Kind code of ref document: T

Effective date: 20210415

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602014076095

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG9D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210630

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210630

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20210331

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1377490

Country of ref document: AT

Kind code of ref document: T

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210802

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210731

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602014076095

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20220104

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210731

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20220131

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220115

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220131

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220131

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220131

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220115

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230523

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20140115

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210331

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20250129

Year of fee payment: 12

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210331

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20260126

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20260127

Year of fee payment: 13